In the past years, we have cloned human Alpha and Beta interferon (IFN) genes and used these DNAs and antisera to Alpha and Beta IFN peptides as specific probes to study molecule mechanism involved in the regulation of IFN genes expression. We have shown that in human cells inducer activates transcription of IFN genes; the difference between the rate of transcription between Alpha and Beta IFN genes was found, however, the kinetic of induction was coordinate. Evidence for the regulation of IFN synthesis on the posttranscriptional level was also found. In cells induced with poly rI.rC, the Beta IFN gene is transcribed in nuclei during the shut-off period when no BetamRNA and BetaIFN synthesis can be detected in cells. In induced lymphoblastoid cells the amount of Beta IFN detected in the medium was 10-fold lower than Chi IFNs. While the relative levels of Chi and Beta mRNA in the cells were similar; a difference in the cellular processing and turnover between these two types of interferons was found. The detail analysis of Beta IFN transcription indicated that the termination may be cell type specific. The Beta IFN gene was also inserted behind strong viral promoters of HSV group and the expression and regulation of these hybrid genes after transfection inheterologous cells was studied. In the present proposal, we plan to examine the role of cis and trans element on the activation and regulation of Beta IFN genes. The expression of endogenous and exogenous genes will be examined in homologous cells of different histological origin. An attempt will be made to develop in vitro assay to identify the regulatory factor involved in the activation or switch-off of IFN genes. We plan to analyze further the termination sites of the primary transcripts of IFN genes, determine the sequence of the termination site(s) and examine whether the termination is cell type or inducer specific. Finally, the question of the regulation of IFN synthesis through the modulation of IFN mRNA stability will be examined and elements essential for the specfic recognition of IFN mRNA by the degradation systems determined.